Regulatory signals from the brain and gut control appetite. Two neuropeptides thought to have a primary role in the hypothalamic feeding centers are neuropeptide Y (NPY), an orexigenic, and cholecystokinin (CCK) a satiety factor. Gut signals appear to act through hypothalamic brain peptides to regulate feeding. Signals sent to the hypothalamus during gastric distension, intestinal passage of nutrients, and postabsorptive sensation of caloric intake, may influence satiety. Unfortunately, the current body of information is not adequate for a full understanding of the neuropeptidergic control of the satiety cascade. Our preliminary experiments in a canine feeding model have begun to clarify some of these central and peripheral satiety signals. This model of cerebroventricular cannulation and true sham feeding in the dog is the basis for the studies detailed in the following seven specific aims: 1. Characterize the central and peripheral effects of NPY on sham feeding and determine whether central NPY is a physiologic stimulator of feeding in the dog. 2. Determine if central NPY is the final event in the initiation of feeding by characterizing its effects against several known satiety signals (i.e., gastric distension, intestinal and intravenous nutrients, central CCK and naloxone). 3. Characterize central CCK's satiety inducing effect against a variety of feeding signals (i.e., starvation, central endorphine and NPY and highly palatable food). 4. Determine whether there is a relationship between the central effect of CCK/NPY on feeding and gastric emptying. 5. Determine whether gastric distension-induced satiety is mediated by the central release of CCK, and if that release is vagal mediated. 6. Determine the effect of intestinal perfusion (jejunal, ileal or colonic) with nutrients (fats, carbohydrates, proteins) on sham feeding. 7. Study the effect of chronic intravenous feeding (fats, carbohydrates, proteins or mixed) versus enteral feeding on sham feeding. From these studies we hope to better understand the relative importance of a variety of signals and eventually construct an integrated satiety cascade. This information is a necessary prerequisite to our understanding of disease processes associated with disturbances in nutrient intake, such as anorexia nervosa and bulemia.